This application proposes the establishment of an Alzheimer's Disease Research Center (ADRC) at UCLA. The theme of the ADRC is "understanding the mechanisms and optimizing the treatment of Alzheimer's disease". An ADRC would add a basic science dimension to established activities of the current UCLA Alzheimer's Disease Core Center (ADCC), use tissues and antibodies from the ADCC Neuropathology Core, and facilitate an invigorating interchange between clinical scientists and the growing cadre of basic scientists at UCLA. The ADCC has accomplished its original goals and established a flow of well characterized patients that are being followed longitudinally (Clinical Core); accessioned 148 brains into the ADCC brain bank (Neuropathology Core); created an imaging archive with sophisticated image analysis techniques available to investigators (Imaging Subcore of Imaging and Genetics Core); developed mechanisms for routine genotyping and established a DNA bank for genetic investigations (Genetics Subcore of Imaging and Genetics Core); and engaged ore than 3600 clinicians in education programs (Education/Information Transfer Core). The ADCC database contains information on 1261 patients and control, in the past year we have achieved an annualized follow-up rate of 90%. In the past five years, we have awarded funding for 12 Pilot Projects; these projects have contributed to 10 funded grants and 22 publications. The ADCC has three clinical sites, each serving a different ethnic population: UCLA (primarily majority culture patients), Martin Luther King Medical Center/Drew Medical School (primarily an African-American population), and Olive View Medical Center (an Hispanic population). UCLA investigators using data from the Cores have advanced understanding of frontotemporal dementias, dementia with Lewy bodies, behavioral aspects of AD, the role of vascular disease in AD and vascular dementia, and the role of imaging and genetics in the diagnosis and characterization of AD. ADCC investigators published 375 articles and 338 abstracts on dementia-related topics between 1993 and 1997. Three basic science projects are being proposed: 1) apolipoprotein influences on amyloid deposition (Greg Cole, Ph.D.), 2) amyloid deposition, toxicity, and inflammation in an amyloid infusion model of AD (Sally Frautschy Ph.D.) and intracellular amyloid signaling (Istvan Mody, Ph.D.). The activities of the Cores will be continued an expanded in the ADRC and the Project Leaders will be integrated into all aspects of the ADRC.